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The relevance of miR‐200 family in the prognosis of digestive system tumors remains controversial. Through a systematic review of the pertinent literature using online databases including PubMed, EMBASE, The Cochrane Library, and Web of Science, our pooled‐analysis revealed that miR‐200 family downregulation was significantly correlated with poor overall survival (OS, hazard ratio [HR] > 1) and disease‐free survival (HR > 1) in digestive malignancies. Consistently, subgroup analyzes of various organ tissues, univariate analysis, gastric cancer, pancreatic cancer, and patients of American descent revealed the hazardous effects of miR‐200 family downregulation. In contrast, low miR‐200 family expression in blood samples predicted favorable OS (HR < 1). Moreover, lower expression levels of miR‐200c‐5p and miR‐429 were validated in esophageal squamous cell carcinoma (ESCC) tissues. Both the protein and messenger RNA expression levels of Paralemmin‐2 (PALM2) and Mitotic Arrest Deficient 2‐Like Protein (MAD2L1), regulated by miR‐200c‐5p, were notably higher in ESCC, and increased protein levels of PALM2 and MAD2L1 were correlated with adverse OS. PALM2 overexpression significantly enhanced ESCC cell migration. In conclusion, our study highlights the prognostic value of miR‐200 family in digestive system tumors, and the decrease of miR‐200c‐5p may promote ESCC invasion through upregulation of PALM2 and MAD2L1.
The relevance of miR‐200 family in the prognosis of digestive system tumors remains controversial. Through a systematic review of the pertinent literature using online databases including PubMed, EMBASE, The Cochrane Library, and Web of Science, our pooled‐analysis revealed that miR‐200 family downregulation was significantly correlated with poor overall survival (OS, hazard ratio [HR] > 1) and disease‐free survival (HR > 1) in digestive malignancies. Consistently, subgroup analyzes of various organ tissues, univariate analysis, gastric cancer, pancreatic cancer, and patients of American descent revealed the hazardous effects of miR‐200 family downregulation. In contrast, low miR‐200 family expression in blood samples predicted favorable OS (HR < 1). Moreover, lower expression levels of miR‐200c‐5p and miR‐429 were validated in esophageal squamous cell carcinoma (ESCC) tissues. Both the protein and messenger RNA expression levels of Paralemmin‐2 (PALM2) and Mitotic Arrest Deficient 2‐Like Protein (MAD2L1), regulated by miR‐200c‐5p, were notably higher in ESCC, and increased protein levels of PALM2 and MAD2L1 were correlated with adverse OS. PALM2 overexpression significantly enhanced ESCC cell migration. In conclusion, our study highlights the prognostic value of miR‐200 family in digestive system tumors, and the decrease of miR‐200c‐5p may promote ESCC invasion through upregulation of PALM2 and MAD2L1.
The Kazakh cattle in the Xinjiang Uygur Autonomous Region of China are highly adaptable and have multiple uses, including milk and meat production, and use as draft animals. They are an excellent original breed that could be enhanced by breeding and hybrid improvement. However, the genomic diversity and signature of selection underlying the germplasm characteristics require further elucidation. Herein, we evaluated 26 Kazakh cattle genomes in comparison with 103 genomes of seven other cattle breeds from regions around the world to assess the Kazakh cattle genetic variability. We revealed that the relatively low linkage disequilibrium at large SNP distances was strongly correlated with the largest effective population size among Kazakh cattle. Using population structural analysis, we next demonstrated a taurine lineage with restricted Bos indicus introgression among Kazakh cattle. Notably, we identified putative selected genes associated with resistance to disease and body size within Kazakh cattle. Together, our findings shed light on the evolutionary history and breeding profile of Kazakh cattle, as well as offering indispensable resources for germplasm resource conservation and crossbreeding program implementation.
Targeting CDC20 can enhance the radiosensitivity of tumor cells, but the function and mechanism of CDC20 on DNA damage repair response remains vague. To examine that issue, tumor cell lines, including KYSE200, KYSE450, and HCT116, were utilized to detect the expression, function, and underlying mechanism of CDC20 in radio-chemoresistance. Western blot and immunofluorescence staining were employed to confirm CDC20 expression and location, and radiation could upregulate the expression of CDC20 in the cell nucleus. The homologous recombination (HR) and non-homologous end joining (NHEJ) reporter gene systems were utilized to explore the impact of CDC20 on DNA damage repair, indicating that CDC20 could promote HR repair and radio/chemo-resistance. In the early stages of DNA damage, CDC20 stabilizes the RPA1 protein through protein-protein interactions, activating the ATR-mediated signaling cascade, thereby aiding in genomic repair. In the later stages, CDC20 assists in the subsequent steps of damage repair by the ubiquitin-mediated degradation of RPA1. CCK-8 and colony formation assay were used to detect the function of CDC20 in cell vitality and proliferation, and targeting CDC20 can exacerbate the increase in DNA damage levels caused by cisplatin or etoposide. A tumor xenograft model was conducted in BALB/c-nu/nu mice to confirm the function of CDC20 in vivo, confirming the in vitro results. In conclusion, this study provides further validation of the potential clinical significance of CDC20 as a strategy to overcome radio-chemoresistance via uncovering a novel role of CDC20 in regulating RPA1 during DNA damage repair.
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